Cell culture media support and maintain the growth of cells in an artificial environment.
Depending on the type of organism whose growth shall be supported, the cell culture media may comprise more than 10, sometimes more than one hundred different components.
The culture media required for the propagation of mammalian, insect or plant cells are typically much more complex than the minimal media sufficient to support the growth of bacteria and yeasts.
Early studies of cell culture utilized media consisting of undefined components, such as plasma, serum, embryo extracts, other non-defined biological extracts or peptones. A major advance was thus made with the development of chemically defined media. Chemically defined media often comprise but are not exclusively limited to amino acids, vitamins, metal ions, antioxidants, chelators, growth factors, buffers, hormones, chlorides and many more substances known to those expert in the art
Some cell culture media are offered as sterile aqueous liquids. The disadvantage of liquid cell culture media is their reduced shelf life and difficulties for shipping and storage. As a consequence, many cell culture media are presently offered as finely milled dry powder mixtures. They are manufactured for the purpose of dissolving in water and/or aqueous solutions and in the dissolved state are designed, often with other supplements, for supplying biological cells with a substantial nutrient base for growth and/or production of biopharmaceuticals from same said cells.
The handling of finely milled powders has significant disadvantages. For example, they are very dusty to handle, more so in large amounts, which can lead to health problems of workers handling the material especially if some of the individual raw materials are hazardous to health. Even if the individual components are not directly toxic there can be health problems caused to workers by high dust levels in the breathable air per se and amounts of dust in air are strictly regulated in many countries due to this problem. Furthermore dust of organic materials, more especially fine dust, can easily result in explosions if amounts are excessive and cautionary measures are not adequate to prevent ignition by sparks.
In addition, it can occur under disadvantageous transport conditions, for example during long transport conditions, that one or more of the lighter individual components of the dry powder media migrates towards the surface or one or more heavier components migrates towards the base of the primary packaging. The result of this local higher concentration or, in the physical centre of the bulk material, the depletion of certain individual component/s, can be negative in many ways on the product quality of the media. In addition, the de-mixing can have effects far beyond physical depletion and concentration of individual components, for example, on target biopharmaceutical molecule production amounts per batch or more subtly on the oligosaccharide patterning on biopharmaceuticals themselves making media quality absolutely critical to biopharmaceutical quality right until the patient.
Another aspect when using finely milled dry powder media is the difficulty to dissolve the fine powder in aqueous solutions to prepare the final aqueous cell culture medium. It is very difficult to wet a finely milled powder and dissolve it in an aqueous liquid. Therefore, the handling of the powder media and their use is quite complicated.
Due to the limitation of dry power media for stability, mixing and dissolving, media in dry format are usually produced without some key supplements such as carbonate, hydrolysates, growth factors and other trace elements, which end users will supplement when they prepare liquid from the dry powder media. The additional handling and supplementing will increase the potential for very costive errors and labour.
It is known that powdered bacterial cell culture media can be granulated by pressing the powder to small granules. The result are small particles with advantages in safety, handling and performance. This procedure can be easily realized for bacterial cell culture media as they comprise chemically poorly defined peptones or tryptones or equivalent peptidic components that support the adherence of the media components through their inherent stickiness.
Mammalian, and/or insect and/or plant cell culture media typically do not contain peptones or their equivalents and are thus much more difficult to handle in this manner.
U.S. Pat. No. 6,383,810 B2 by Invitrogen Corporation discloses a method of producing an agglomerated eukaryotic cell culture medium powder. The method comprises wetting a dry powder cell culture medium with a solvent and then re-drying the moistened medium to obtain a dry agglomerated cell culture medium.
A great disadvantage of this procedure is the fact that the whole medium components need to be contacted with water and that they need to be heated to remove the water afterwards. This may cause considerable side reactions among the components of the medium or destruction or modification of sensitive components with an unpredictable outcome on the medium quality.
Consequently, there exists a clear need for finding a new form of mammalian, and/or insect and/or plant cell culture media which is easy to handle and can be produced without causing destruction and/or side reactions among the medium components.